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miR-1254 通过靶向 CD36 在口腔鳞状细胞癌中发挥肿瘤抑制作用。

MiR-1254 Functions as a Tumor Suppressor in Oral Squamous Cell Carcinoma by Targeting CD36.

机构信息

1 Department of Oral Medicine, The Key Laboratory of Stomatology, College and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, Hebei, China.

2 Department of Oral & Maxillofacial Surgery, The Key Laboratory of Stomatology, College and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, Hebei, China.

出版信息

Technol Cancer Res Treat. 2019 Jan 1;18:1533033819859447. doi: 10.1177/1533033819859447.

Abstract

Oral squamous cell carcinoma is one of the most common cancers around the world. The patients with oral squamous cell carcinoma are often diagnosed at late stages, leading to unfavorable prognosis. MicroRNAs might function as oncogenes or tumor suppressor genes in the tumorigenesis of cancer. This study aimed to explore the role of miR-1254 in oral squamous cell carcinoma. We examined the expression levels of miR-1254 in oral squamous cell carcinoma tissue samples and cell line.Proliferation and invasion assays were performed in oral squamous cell carcinoma cells with miR-1254 overexpression or underexpression. The potential regulatory mechanisms were also explored. We found that miR-1254 was significantly reduced in oral squamous cell carcinoma tissues and cell lines. In addition, downregulation of miR-1254 in oral squamous cell carcinoma tumor tissues was closely associated with cancer staging and lymph node metastasis. Enforced expression of miR-1254 significantly inhibited proliferation and invasion in oral cancer cells, and downregulation of miR-1254 promoted the oncogenic activities of oral cancer cells. CD36 was identified as a direct downstream target of miR-1254 by the luciferase reporter assay. Overexpression of CD36 partially restored the proliferation and invasion capacity inhibited by miR-1254. CD36 expression was inversely correlated with miR-1254 expression in the oral squamous cell carcinoma tissues. Taken together, our study provided the compelling evidence that miR-1254 might inhibit the progression of OSCC by partially downregulating CD36, and restoration of miR-1254 may represent an effective strategy for treating oral squamous cell carcinoma.

摘要

口腔鳞状细胞癌是全球最常见的癌症之一。口腔鳞状细胞癌患者通常在晚期被诊断,导致预后不佳。miRNA 可能在癌症的肿瘤发生中作为癌基因或肿瘤抑制基因发挥作用。本研究旨在探讨 miR-1254 在口腔鳞状细胞癌中的作用。我们检测了口腔鳞状细胞癌组织样本和细胞系中 miR-1254 的表达水平。在口腔鳞状细胞癌细胞中过表达或下调 miR-1254 后进行增殖和侵袭实验。还探索了潜在的调节机制。我们发现 miR-1254 在口腔鳞状细胞癌组织和细胞系中显著降低。此外,口腔鳞状细胞癌肿瘤组织中 miR-1254 的下调与癌症分期和淋巴结转移密切相关。miR-1254 的过表达显著抑制了口腔癌细胞的增殖和侵袭,而下调 miR-1254 则促进了口腔癌细胞的致癌活性。通过荧光素酶报告实验鉴定出 CD36 是 miR-1254 的直接下游靶标。CD36 的过表达部分恢复了 miR-1254 抑制的增殖和侵袭能力。CD36 的表达与口腔鳞状细胞癌组织中的 miR-1254 表达呈负相关。综上所述,我们的研究提供了令人信服的证据,表明 miR-1254 可能通过部分下调 CD36 抑制 OSCC 的进展,恢复 miR-1254 可能代表治疗口腔鳞状细胞癌的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c83c/6691659/33eda3883bab/10.1177_1533033819859447-fig1.jpg

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